
The compound of formula (I) is known as sildenafil with the chemical name of 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulphonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one. The compound was originally used in the treatment for certain cardiovascular diseases, such as angina, hypertension, heart failure, atherosclerosis and so on. Later it was found that this compound was particularly useful in the treatment for men erectile dysfunction.
Sildenafil is a selective phosphodiesterase type 5 inhibitor. This compound and its preparation method were originally disclosed in Chinese patent application CN 1,057,464A (corresponding to European patent application EP-A 463,756), and it has been found that this compound is useful in the treatment of certain cardiovascular disease. The use of sildenafil in the treatment for men erectile dysfunction was first disclosed in Chinese patent application CN 1,124,926A. An improved process for the preparation of sildenafil is described in a later application, Chinese patent application CN 1,168,376A (corresponding to EP-A 812845). CN 1,208,337C discloses a process for the preparation of sildenafil in the presence of an inorganic oxidant. Two kinds of sildenafil intermediates and processes for their preparations are described in CN 1,176,081C and CN 1,281,851A respectively. A process for the synthesis of sildenafil with a resin is also described in prior art Bioorg. Med. Chem. Lett. 2000, 10, 1983-1986. U.S. Pat. No. 6,204,383 discloses another process for the preparation of sildenafil, wherein a less basic intermediate is used and finally, a methylamine is used to close the piperazine ring to give sildenafil. In WO 2001/019827, it provides a process for the preparation of sildenafil by a methylation with formaldehyde.
Most of the processes for the preparation of sildenafil in the prior art have side-reactions, resulting in a reduced yield of the final product, which have some limitation on pharmaceutical industry.